Incorporated fish oil fatty acids prevent action potential shortening induced by circulating fish oil fatty acids

Increased consumption of fatty fish, rich in omega-3-polyunsaturated fatty acids(omega 3-PUFAs) reduces the severity and number of arrhythmias. Long-term omega 3-PUFA-intake modulates the activity of several cardiac ion channels leading to cardiac action potential shortening. Circulating omega 3-PUFAs in the bloodstream and incorporated omega 3-PUFAs in the cardiac membrane have a different mechanism to shorten the action potential. It is, however, unknown whether circulating omega 3-PUFAs in the bloodstream enhance or diminish the effects of incorporated omega 3-PUFAs. In the present study, we address this issue. Rabbits were fed a diet rich in fish oil (omega 3) or sunflower oil (omega 9, as control) for 3 weeks. Ventricular myocytes were isolated by enzymatic dissociation and action potentials were measured using the perforated patch-clamp technique in the absence and presence of acutely administered omega 3-PUFAs. Plasma of omega 3 fed rabbits contained more free eicosapentaenoic acid (EPA) and isolated myocytes of omega 3 fed rabbits contained higher amounts of both EPA and docosahexaenoic acid (DHA) in their sarcolemma compared to control. In the absence of acutely administered fatty acids, omega 3 myocytes had a shorter action potential with a more negative plateau than omega 9 myocytes. In the omega 9 myocytes, but not in the omega 3 myocytes, acute administration of a mixture of EPA + DHA shortened the action potential significantly. From these data we conclude that incorporated omega 3-PUFAs into the sarcolemma and acutely administered omega 3 fatty acids do not have a cumulative effect on action potential duration and morphology. As a consequence, patients with a high cardiac omega 3-PUFA status will probably not benefit from short term omega 3 supplementation as an antiarrhythmic therapy.